The prevalence and burden of subthreshold generalized anxiety disorder: a systematic review

BackgroundTo review the prevalence and impact of generalized anxiety disorder (GAD) below the diagnostic threshold and explore its treatment needs in times of scarce healthcare resources.MethodsA systematic literature search was conducted until January 2013 using PUBMED/MEDLINE, PSYCINFO, EMBASE and reference lists to identify epidemiological studies of subthreshold GAD, i.e. GAD symptoms that do not reach the current thresholds of DSM-III-R, DSM-IV or ICD-10. Quality of all included studies was assessed and median prevalences of subthreshold GAD were calculated for different subpopulations.ResultsInclusion criteria led to 15 high-quality and 3 low-quality epidemiological studies with a total of 48,214 participants being reviewed. Whilst GAD proved to be a common mental health disorder, the prevalence for subthreshold GAD was twice that for the full syndrome. Subthreshold GAD is typically persistent, causing considerably more suffering and impairment in psychosocial and work functioning, benzodiazepine and primary health care use, than in non-anxious individuals. Subthreshold GAD can also increase the risk of onset and worsen the course of a range of comorbid mental health, pain and somatic disorders; further increasing costs. Results are robust against bias due to low study quality.ConclusionsSubthreshold GAD is a common, recurrent and impairing disease with verifiable morbidity that claims significant healthcare resources. As such, it should receive additional research and clinical attention.

[1]  A. House,et al.  Depression and Anxiety Impair Health-Related Quality of Life and Are Associated With Increased Costs in General Medical Inpatient , 2002 .

[2]  K. O'Connor,et al.  The epidemiology of specific phobia and subthreshold fear subtypes in a community‐based sample of older adults , 2011, Depression and anxiety.

[3]  H. Möller,et al.  Subsyndromale Angststörungen: Definition, Messparameter, Epidemiologie , 2009 .

[4]  Olga V. Demler,et al.  The US National Comorbidity Survey Replication (NCS‐R): design and field procedures , 2004, International journal of methods in psychiatric research.

[5]  R. Judge,et al.  Patient perspectives on once-weekly fluoxetine. , 2001, The Journal of clinical psychiatry.

[6]  J. Angst Depression and anxiety: implications for nosology, course, and treatment. , 1997, The Journal of clinical psychiatry.

[7]  P. Cuijpers,et al.  Subthreshold depression as a risk indicator for major depressive disorder: a systematic review of prospective studies , 2004, Acta psychiatrica Scandinavica.

[8]  John R Seeley,et al.  Subthreshold conditions as precursors for full syndrome disorders: a 15-year longitudinal study of multiple diagnostic classes. , 2009, Journal of child psychology and psychiatry, and allied disciplines.

[9]  I. Olkin,et al.  Meta-analysis of observational studies in epidemiology - A proposal for reporting , 2000 .

[10]  W. Maier,et al.  Selection bias during recruitment of elderly subjects from the general population for psychiatric interviews , 2008, European Archives of Psychiatry and Clinical Neuroscience.

[11]  W. Maier,et al.  Prevalence and recognition of anxiety syndromes in five European primary care settings , 1998, British Journal of Psychiatry.

[12]  C. Brayne,et al.  Co‐occurrence of anxiety and depressive disorders in a community sample of older people: results from the MRC CFAS (Medical Research Council Cognitive Function and Ageing Study) , 2008, International journal of geriatric psychiatry.

[13]  J. Hoyer,et al.  Generalized anxiety disorder: nature and course. , 2001, The Journal of clinical psychiatry.

[14]  M. Gatz,et al.  DSM-IV criteria for generalized anxiety disorder in older adults: distinguishing the worried from the well. , 2003, Psychology and aging.

[15]  JianLi Wang,et al.  The Epidemiology of Mental and Substance Use—Related Disorders among White, Chinese, and other Asian Populations in Canada , 2006, Canadian journal of psychiatry. Revue canadienne de psychiatrie.

[16]  L W Chambers,et al.  Critical appraisal of the health research literature: prevalence or incidence of a health problem. , 1998, Chronic diseases in Canada.

[17]  A. Okasha Would the use of dimensions instead of categories remove problems related to subthreshold disorders? , 2009, European Archives of Psychiatry and Clinical Neuroscience.

[18]  F. Smit,et al.  Cost-effectiveness of a stepped care intervention to prevent depression and anxiety in late life: randomised trial , 2010, British Journal of Psychiatry.

[19]  K. O'Connor,et al.  The impact of DSM-IV symptom and clinical significance criteria on the prevalence estimates of subthreshold and threshold anxiety in the older adult population. , 2011, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[20]  H. Wittchen,et al.  Prevalence of mental disorders and psychosocial impairments in adolescents and young adults , 1998, Psychological Medicine.

[21]  P. Brantley,et al.  Subsyndromal (“Mixed”) anxiety-depression in primary care , 1994, Journal of General Internal Medicine.

[22]  R. Kessler,et al.  Understanding mental health treatment in persons without mental diagnoses: results from the National Comorbidity Survey Replication. , 2007, Archives of general psychiatry.

[23]  P. Cuijpers,et al.  Prevention of late-life anxiety and depression has sustained effects over 24 months: a pragmatic randomized trial. , 2011, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[24]  D. Stein,et al.  Consensus statement on generalized anxiety disorder from the International Consensus Group on Depression and Anxiety. , 2001, The Journal of clinical psychiatry.

[25]  H. Wittchen,et al.  Prevalence and 12-month outcome of threshold and subthreshold mental disorders in primary care. , 1999, Journal of affective disorders.

[26]  A. House,et al.  Depression and anxiety impair health-related quality of life and are associated with increased costs in general medical inpatients. , 2002, Psychosomatics.

[27]  A. Gamma,et al.  The generalized anxiety spectrum: prevalence, onset, course and outcome , 2009, European Archives of Psychiatry and Clinical Neuroscience.

[28]  Dan J Stein,et al.  Rethinking the duration requirement for generalized anxiety disorder: evidence from the National Comorbidity Survey Replication , 2005, Psychological Medicine.

[29]  Ipsit V Vahia,et al.  A tune in "a minor" can "b major": a review of epidemiology, illness course, and public health implications of subthreshold depression in older adults. , 2011, Journal of affective disorders.

[30]  K Kroenke,et al.  Health-related quality of life in primary care patients with mental disorders. Results from the PRIME-MD 1000 Study. , 1995, JAMA.

[31]  P. Cuijpers,et al.  Psychological treatments of subthreshold depression: a meta‐analytic review , 2007, Acta psychiatrica Scandinavica.

[32]  J. Coyne,et al.  Nondetection of depression by primary care physicians reconsidered. , 1995, General hospital psychiatry.

[33]  A. Beck,et al.  Generalized Anxiety Disorder: Between Neglect and an Epidemic , 2012, The Journal of nervous and mental disease.

[34]  S. Rosi,et al.  The epidemiology of panic disorder and agoraphobia in Europe , 2005, European Neuropsychopharmacology.

[35]  A. V. van Balkom,et al.  Consequences of anxiety in older persons: its effect on disability, well-being and use of health services , 1999, Psychological Medicine.

[36]  J. Smit,et al.  Consequences of major and minor depression in later life: a study of disability, well-being and service utilization , 1997, Psychological Medicine.

[37]  COURSE AND RISK FACTORS OF FUNCTIONAL IMPAIRMENT IN SUBTHRESHOLD DEPRESSION AND ANXIETY , 2013, Depression and anxiety.

[38]  A. Papassotiropoulos,et al.  Subthreshold depressive and anxiety disorders in the elderly. , 2000, European psychiatry : the journal of the Association of European Psychiatrists.

[39]  W. Maier,et al.  The relationship between major and subthreshold variants of unipolar depression. , 1997, Journal of affective disorders.

[40]  A. Gamma,et al.  Subjective distress predicts treatment seeking for depression, bipolar, anxiety, panic, neurasthenia and insomnia severity spectra , 2010, Acta psychiatrica Scandinavica.

[41]  H. Möller,et al.  Silexan, an orally administered Lavandula oil preparation, is effective in the treatment of ‘subsyndromal’ anxiety disorder: a randomized, double-blind, placebo controlled trial , 2010, International Clinical Psychopharmacology.

[42]  A. Gamma,et al.  Varying temporal criteria for generalized anxiety disorder: prevalence and clinical characteristics in a young age cohort , 2006, Psychological Medicine.

[43]  J. Füredi,et al.  Anxiety and mood disorders in primary care practice , 2004, International journal of psychiatry in clinical practice.

[44]  M V Mendlowicz,et al.  Quality of life in individuals with anxiety disorders. , 2000, The American journal of psychiatry.

[45]  R. Kessler,et al.  Patterns and correlates of generalized anxiety disorder in community samples. , 2002, The Journal of clinical psychiatry.

[46]  H. Helmchen,et al.  Subthreshold disorders in psychiatry: clinical reality, methodological artifact, and the double-threshold problem. , 2000, Comprehensive psychiatry.

[47]  P. Cuijpers,et al.  Early intervention in panic: pragmatic randomised controlled trial , 2010, British Journal of Psychiatry.

[48]  BMC Psychiatry , 2007 .

[49]  Y. Lecrubier,et al.  An international study of psychological problems in primary care. Preliminary report from the World Health Organization Collaborative Project on 'Psychological Problems in General Health Care'. , 1993, Archives of general psychiatry.

[50]  C. Hudon,et al.  Anxiety disorders, depressive episodes and cognitive impairment no dementia in community‐dwelling older men and women , 2011, International journal of geriatric psychiatry.

[51]  N Sartorius,et al.  Depression Comorbid with Anxiety: Results from the WHO Study on Psychological Disorders in Primary Health Care , 1996, British Journal of Psychiatry.

[52]  G. Nestadt,et al.  Characterizing generalized anxiety: temporal and symptomatic thresholds. , 1998, The Journal of nervous and mental disease.

[53]  S. Shankman,et al.  Family study of subthreshold psychopathology in a community sample , 2007, Psychological Medicine.

[54]  S. Shankman,et al.  The prevalence and co-morbidity of subthreshold psychiatric conditions , 2004, Psychological Medicine.

[55]  K. Wells,et al.  Clinical and subthreshold panic disorder , 2010, Depression and anxiety.

[56]  R. Kessler,et al.  Broadening the definition of generalized anxiety disorder: effects on prevalence and associations with other disorders in the National Comorbidity Survey Replication. , 2007, Journal of anxiety disorders.

[57]  D H Barlow,et al.  Mixed anxiety-depression and its implications for models of mood and anxiety disorders. , 2000, Comprehensive psychiatry.

[58]  K. Kroenke,et al.  Outcome and Impact of Mental Disorders in Primary Care at 5 years , 2007, Psychosomatic medicine.

[59]  R. C. Hall,et al.  Global assessment of functioning. A modified scale. , 1995, Psychosomatics.

[60]  M. Höfler,et al.  Estimating the prevalence of mental and somatic disorders in the community: aims and methods of the German National Health Interview and Examination Survey , 2002, International journal of methods in psychiatric research.

[61]  M. Tansella,et al.  Subthreshold psychiatric disorders in primary care: prevalence and associated characteristics. , 2003, Journal of affective disorders.

[62]  J. Garber,et al.  The temporal relation between depression and comorbid psychopathology in adolescents at varied risk for depression. , 2010, Journal of child psychology and psychiatry, and allied disciplines.

[63]  M. Ansseau,et al.  High prevalence of mental disorders in primary care. , 2004, Journal of affective disorders.

[64]  J. Angst,et al.  The Zurich study —A prospective epidemiological study of depressive, neurotic and psychosomatic syndromes , 2004, European archives of psychiatry and neurological sciences.

[65]  W. Maier,et al.  Generalized anxiety disorder (ICD‐10) in primary care from a cross‐cultural perspective: a valid diagnostic entity? , 2000, Acta psychiatrica Scandinavica.

[66]  M. Höfler,et al.  Generalized anxiety and depression in primary care: prevalence, recognition, and management. , 2002, The Journal of clinical psychiatry.

[67]  M. Höfler,et al.  Association between generalized anxiety levels and pain in a community sample: evidence for diagnostic specificity. , 2009, Journal of anxiety disorders.

[68]  J Ormel,et al.  Health care costs associated with depressive and anxiety disorders in primary care. , 1995, The American journal of psychiatry.

[69]  D. Ford,et al.  Depression and Risk for Onset of Type II Diabetes: A prospective population-based study , 1996, Diabetes Care.

[70]  J. Hoyer,et al.  Generalized anxiety disorder and clinical worry episodes in young women , 2002, Psychological Medicine.

[71]  P. Rucci,et al.  Mental, Physical and Functional Status in Primary Care Attenders , 1999, International journal of psychiatry in medicine.

[72]  M. Olfson,et al.  Subthreshold psychiatric symptoms in a primary care group practice. , 1996, Archives of general psychiatry.

[73]  R. Kessler,et al.  One‐year prevalence of subthreshold and threshold DSM‐IV generalized anxiety disorder in a nationally representative sample , 2001, Depression and anxiety.

[74]  S. Kertz,et al.  Human and Economic Burden of GAD, Subthreshold GAD, and Worry in a Primary Care Sample , 2011, Journal of Clinical Psychology in Medical Settings.

[75]  N. Singleton,et al.  Panic disorder and subthreshold panic in the UK general population: Epidemiology, comorbidity and functional limitation , 2011, European Psychiatry.

[76]  H. Wittchen,et al.  Associations of familial risk factors with social fears and social phobia: evidence for the continuum hypothesis in social anxiety disorder? , 2008, Journal of Neural Transmission.

[77]  J. Rabe-Jabłońska,et al.  [Affective disorders in the fourth edition of the classification of mental disorders prepared by the American Psychiatric Association -- diagnostic and statistical manual of mental disorders]. , 1993, Psychiatria polska.